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WHAT IS THE NEW CLASSIFICATION SYSTEM FOR LYMPHATIC MALFORMATIONS?

• This was reclassified in 2014 at the International Society for the Study of Vascular Anomalies (ISSVA) [1]. 
• They are now stratified based on genomic testing and hematic mutations.
• The current classification of lymphatic malformations are:
• Cystic
• Macrocystic lymphatic malformation
• Microcystic lymphatic malformation
• Mixed cystic lymphatic malformation
• Generalized lymphatic anomaly
• These have bone, soft tissue or internal organ involvement.
• Lymphatic malformation in Gorham-Stout disease
• This has bone involvement.
• Channel Type lymphatic malformations
• The rest of the classification system can be found on the ISSVA website: http://www.issva.org/classification.
• How does the new classification system help clinically?
• There have been many decades of confusion because of using incorrect or inconsistent names. This new classification system allows for improved and consistent communication between providers and patients. Using inconsistent or incorrect names will confuse fellow colleagues, as well as the patients.

CASE: TRUNCAL MASS

• A 2-year-old patient is referred for a truncal mass on the chest that is soft, and without overlying skin changes. An ultrasound shows multiple cysts.
• Work-Up:
• It is important to have an interdisciplinary team, so there will always be a group of experts working together to make the diagnosis and the plan.
• First step is to perform a detailed history and physical exam.
• Evaluate for other lesions.
• If the lesion appears superficial and isolated to one area, at Boston Children’s Hospital, an interventional radiologist will perform an ultrasound in the clinic, and the team can then decide the appropriate treatment.  
• Role of surgery:
• Most lymphatic malformations are visible at birth, so this could be a 2-year-old who is presenting with a suddenly expanding lesion, but you should also consider other anomalies such as a sarcoma, teratoma, infectious lesion, etc.
• If this is really a lymphatic malformation, the management depends on the expertise available.
• About 20-25 years ago, there were not as many options, so surgeons performed more resections.
• There is now a range of available therapies.
• Management:
• There are 4 options for this patient:
1. Observation and reassurance
• These are not cancers and are often not dangerous.
2. Micro-interventional therapy:
• Sclerotherapy may be performed by interventional radiology.
• If IR is not available, especially in other parts of the world, then some surgeons will perform this procedure with ultrasound or other imaging.
• It is important that whoever performs the sclerotherapy has a good understanding of the side effects of each of the sclerotherapy agents.
3. Surgical resection by surgeon
4. Pharmacologic therapy
• If the lesion is relatively small:
• If interventional radiology is confident that the lesion may improve with one to two sclerotherapy sessions, then this should be considered first as it does not leave a scar and is less invasive.
• If the lesion is very small, then surgery should be considered, especially if it will not result in a poor cosmetic scar.
• Surgery has an longer lasting effect compared to sclerotherapy. 
• If the lesion is large:
• These can extend from the torso into the pelvis and are made up of macrocysts. Each one of these macrocysts are accessible to sclerotherapy. Sclerotherapy is an option but it may take several episodes and end up requiring high amounts of radiation for imaging. Also, even if you are able to shrink down the cysts with sclerotherapy, if the lesion is large enough, then it may leave the patient with a lot of redundant skin and a resulting mass.
• So in these cases, surgery may be a better option.
• What medical therapy options are available for large lesions, and when should they be given in relation to surgery?
• Sirolimus, an M-tor inhibitor, is now being used for lymphatic malformations. These block the PIK3CA pathway, which has been shown to be a somatic mutation in a lot of lymphatic malformations and some of the more complicated disorders of lymphatics [2].
• Sirolimus was used initially for the most complicated lymphatic anomalies, and it has really improved the quality of life of patients, by improving pain and decreasing the frequency of infections for the most complicated patients.
• It needs to be used in a controlled manner with good supportive care.
• If there is a complicated lymphatic anomaly, then recommend starting medical therapy before interventional radiology or a surgical procedure. 
• These medications may soften and shrink the lymphatic anomaly, making the procedure less extensive.
• These medications make the resection easier, allowing you to resect extra bulk, and make the flaps be more pliable allowing for a good closure.
• Some recommend stopping the medication prior to surgery to decrease risk of surgical infections.
• For purely macrocytic lesions, it might be easier to operate on when they are big, so it is not recommended to use sirolimus. But for microcystic lesions or complex lesions for debulking, sirolimus is a great adjunct.

WHAT ARE THE CHANCES OF A SMALL LESION GOING AWAY? 

• Most of the lesions that are seen are not going to go away, and it is very rare for pure macro cystic lesions to empty and not re-inflate. But there are a couple of lymphatic lesions that may disappear, although the underlying tissue anomaly may still be present.
• Congenital Lymphedema of lower extremities in infants may also regress to non-detection on physical exam, but this is uncommon.

WHEN IS OBSERVATION OK?

• If the lesion is not impinging on the airway, then it is ok to observe the lesion, especially now because of the increasing concern of early anesthesia on neurodevelopment.
• If it is in the airway, and if it becomes infected or bleeds, this may cause an airway emergency, so these should be treated immediately.
• Making the choice to not do something initially and observe does not eliminate the choice to do something later.
• Also certain lesions, like microcystic lesions of face, tongue or floor of the mouth, are better to treat earlier in infancy for better long-term results, but these treatments are usually medical and not surgical.

WHAT DOES OBSERVATION MEAN?

• The first step is to have a planned algorithm for individual needs, and make sure to assess the financial situation and geography of each patient.
• You may also be able to follow-up with patients with videos and pictures, and Boston Children’s Hospital multidisciplinary team follows these patients closely and decides when is the best time to bring them back to clinic.
• If the patient is local, then recommend follow-up every 6 months to 1 year.
• This depends on the patient. If it is a newborn and new parents, in order to reassure the parents, recommend seeing them every month initially, and then spread it out to 3 months, 6 months and then 1 year. 

WHAT IMAGING SHOULD BE PERFORMED?

• The first imaging modality that should be obtained is ultrasound with Doppler Flow.
• If you still cannot properly assess the lesion, then the next step is an MRI.
• If still cannot determine what the lesion is, then obtain a tissue biopsy.

HOW DOES SCLEROTHERAPY WORK? 

• How many treatments does sclerotherapy require?
• This depends on the size and type of lesion.
• Some patients are treated with just one sclerotherapy session, while others need two to three. 
• Patients may also require additional treatments later on if the lesions recur. 
• First direct treatment to the lesions that are symptomatic (i.e. pain, infection).
• What are the steps of sclerotherapy?
• Aspirate first once you enter the cyst. 
• If this is a venous malformation, you need to make sure it does not extend intravascularly.
• This should be done under fluoroscopy. Inject contrast into the lesion first to make sure it stays in the lesion. You can also consider doing venous mapping before.
• Especially if it is a large lesion, as they have a large capacitance area of abnormal veins, and some have direct macroscopic outflow to a large systemic vein. This can result in pulmonary embolism of the clot induced by sclerotherapy.
• A small amount of ethanol, although ethanol is not used often anymore for sclerotherapy, can case fatal pulmonary hypertension.
• If you have a large vein that has a direct connection to systemic veins, then you need to obliterate the outflow first using endovenous laser simultaneously, titanium coals, glue, etc. 
• What medications are used for sclerotherapy?
• It depends if the lesion has a lymphatic or venous component.
• For macrocystic lesions, doxycycline is used [3].
• For microcystic lesions, bleomycin is now being used, but this needs to be monitored closely for side effects [4].
• If the lesion has a venous component, then sodium tetradecyl sulfate is used.

RESOURCES

• It is important to know when to refer a patient and when to get additional information.
• Please call the Vascular Anomaly Center at Boston Children’s Hospital for any assistance or information at 617-355-5226 or email vascular@childrens.harvard.edu
• Website: www.childrenshospital.org/vascular

REFERENCES

[1]         Wassef M, Blei F, Adams D, et al. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies. PEDIATRICS. 2015;136(1):e203-e214. doi:10.1542/peds.2014-3673

[2]         Luks VL, Kamitaki N, Vivero MP, et al. Lymphatic and Other Vascular Malformative/Overgrowth Disorders Are Caused by Somatic Mutations in PIK3CA. J Pediatr. 2015;166(4):1048-1054.e5. doi:10.1016/j.jpeds.2014.12.069

[3]         Burrows PE, Mitri RK, Alomari A, et al. Percutaneous Sclerotherapy of Lymphatic Malformations with Doxycycline. Lymphat Res Biol. 2008;6(3-4):209-216. doi:10.1089/lrb.2008.1004

[4]         Chaudry G, Guevara CJ, Rialon KL, et al. Safety and Efficacy of Bleomycin Sclerotherapy for Microcystic Lymphatic Malformation. Cardiovasc Intervent Radiol. 2014;37(6):1476-1481. doi:10.1007/s00270-014-0932-z